A Pilot Clinical Study Evaluating the Effect of Parathyroid Hormone (PTH) Lowering On Erythropoietin Consumption in Calcitriol-Resistant Patients

AbbVie (prior sponsor, Abbott)65 enrolled

Overview

To evaluate the effect of PTH lowering on erythropoietin consumption in calcitriol-resistant patients with stage 5 chronic kidney disease.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Moderate to Severe Secondary Hyperparathyroidism Stage 5 Chronic Kidney Diseases

Interventions

ParicalcitolDRUG

Paricalcitol was administered by intravenous bolus. The initial dose was calculated according to the following formula: \[Paricalcitol (µg) = iPTH (pg/mL) / 80\]. Subsequent doses were determined based on iPTH, calcium and phosphorus levels.

Darbepoetin alfaDRUG

Routine darbepoetin alfa use was allowed when transferrin saturation (TSAT) was ≥ 20% and ferritin ≥ 200 μg/L, and hemoglobin level \< 11.5 g/dL. The initial dose was 0.25 to 0.75 µg/kg/week, and the maintenance dose was 0.13 to 0.35 µg/kg/week. Target hemoglobin level was between 10 to 11.5 g/dL.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: A subject will only be included if all the following entry criteria are met: * Patients ≥ 18 years of age * Stage 5 chronic kidney disease (CKD) patients receiving hemodialysis and with moderate to severe secondary hyperparathyroidism (SHPT) * Patients with anemia due to renal insufficiency but who are iron replete:; Transferrin saturation (TSAT) \> 20% and Ferritin levels \> 200 ng/mL and requiring treatment with erythropoietin (EPO) * Patients with vitamin B levels \> lower limit of normal (LLN) and folic acid levels \> LLN * Patients treated only with intravenous calcitriol for at least 6 months * Patients with serum intact parathyroid hormone (iPTH) level \> 500 pg/mL * Patients with calcium phosphate product (Ca × PO4) \< 65 mg²/dL² * Patients willing to sign "written informed consents" before participating in any the study related activity. * Patients with phosphorus levels \< 6.5 mg/dL and calcium levels \< 11.2 mg/dL Exclusion Criteria: A subject will be excluded from the study if he/she meets any of the following criteria: * Patients who have known hypersensitivity and/or toxicity to vitamin D metabolites and/or to paricalcitol and/or to other product ingredients. * Patients who have participated in a clinical study within the last month. * Patients whose previous concomitant medication and laboratory data for 6 months prior to the baseline visit are not available. * Patients with known contraindication to selective Vitamin D receptor activators (VDRAs) according to the Summary of Product Characteristics (SmPC). * Pregnancy, breast-feeding or planning a pregnancy within next 6 months after enrollment. Sexually active female patients not accepting appropriate contraceptive methods during the course of the study will also be excluded. * Hypertensive and diabetic patients who are not on an optimal and steady medication regimen for more than 30 days. * Patients with microcytic (mean corpuscular volume \[MCV\] \< 80 fL) and macrocytic (MCV \> 100 fL) anemia at screening that may be caused by diseases such as for microcytic anemias - Iron Deficiency, Thalassemias, Anemia of Chronic Disease, Copper Deficiency, Zinc poisoning, Sideroblastic Anemia, macrocytic anemias -ethanol abuse, myelodysplastic syndromes, acute myeloid leukemias, reticulocytosis, drug induced anemia, liver disease.

Outcomes

Primary Outcomes

Mean Erythropoietin Dose Per Visit

The requirement of erythropoietin (EPO) treatment to maintain serum hemoglobin levels between 10 to 11.5 g/dL during the study was assessed by analysis of the dose of darbepoetin alfa used at baseline and during each month of the study. The mean EPO dosage per injection for each study month is reported.

Time frame: Baseline and Months 1, 2, 3, 4, 5 and 6

Secondary Outcomes

Mean Scores of Short Form Health Survey 36 (SF-36) Questionnaire

The Medical Outcome Study Short Form 36-Item Health Survey (SF-36) is a self-administered questionnaire that measures the impact of disease on overall quality of life and consists of 36 questions in eight domains. The domains include physical (physical functioning, role limitations due to physical health (role-physical), general health perceptions and pain) and mental domains (energy/fatigue (vitality), social functioning, emotional well-being (mental health), and role limitations due to emotional problems (role emotional)). The individual domain scores are calculated and transformed to range from 0 to 100, with higher scores indicating a better level of functioning.